The NMDP was established in 1987 to (1) create a registry of volunteer, tissue-typed, unrelated bone marrow donors and (2) facilitate matched unrelated donor marrow transplants through a coordinated circuit of Donor Centers, Collection Centers, and Transplant Centers. As of July 1997, 2.7 million donors were participating in the registry and 5,700 unrelated marrow transplants had been performed. The rate of non-engraftment and graft rejection in unrelated-donor transplants varies from 6% to 40%, depending on the degree of HLA matching between the donor and recipient and on whether graft engineering to remove T cells was performed. In recipients with non-engraftment or early graft loss, the best option for therapy is often another dose of stem cells from the original marrow donor. For the first 9 years of the program, consent was sought from the original donor for a second marrow harvest in this setting. More recently, it has been appreciated that peripheral blood-derived stem cell (PBSC) transplants, harvested by apheresis of filgrastim (granulocyte colony- stimulating factor) stimulated donors, can provide larger numbers of hematopoietic progenitor cells that engraft more rapidly than marrow- derived cells. This is particularly true in NMDP donors undergoing a second donation: their marrow is still somewhat depleted of progenitor cells, the sites of marrow harvest are still quite painful, and the recipient is often critically ill and needs hematopoietic reconstitution as rapidly as possible. For these reasons, a protocol involving all participating NMDP Donor Centers was initiated in February 1997 for the acquisition of PBSC's for second transplants. The objectives of the study are (1) to monitor the immediate and long-term safety/sequelae of filgrastim administration in healthy volunteer donors; (2) to compare donor tolerance of, psychosocial response to, and adverse effects of first donations of marrow versus second donations of PBSCs; (3) to determine the efficacy and stem cell content of filgrastim-mobilized PBSC collections; and (4) to monitor the outcome of matched unrelated-donor PBSC transplants, in terms of time to engraftment, incidence of acute and chronic GVHD, and disease-free and overall survival. Donors will be given filgrastim 10 ucg/kg/day SQ for 5 days, with apheresis performed on days 5 and 6. Follow-up clinical and laboratory analysis of the donor will continue annually for a total of 5 years. Thus far, only 4 NMDP donors have donated PBSC's on this protocol, with insufficient data for analysis at this time. The NIH Marrow Donor Center, a participant in the NMDP, has 44,000 donors on its registry. 168 NIH unrelated donors to date have undergone marrow harvest for an NMDP recipient. It is estimated that 2 to 3 NIH donors per year will be enrolled in this second donation study. Two of the principal investigators for this study are in the DTM, CC (S.F.L. and D.S.). Administrative and statistical support for the study is provided by the NMDP National Office. Filgrastim is provided under an IND agreement with Amgen (BB-IND # 6821). The IND is held by the NMDP National Office.